Feasibility of Electroporation in Bone and in the Surrounding Clinically Relevant Structures

Abstract

Skeletal metastases are a common cause of severe morbidity, reduction in quality of life and often early mortality. Consequently, improvements in therapies are necessary. Electroporation uses electric energy to alter cancer cell membrane permeability and enhance the local uptake of chemotherapeutics, thus leading to local tumor control. The aim of this study was to investigate the feasibility and safety of delivering electric field protocols causing electroporation of healthy bone and structures of clinical relevance using small and large animal models. Reversible electroporation was used in the rabbit sciatic nerve by applying 2 series of 8 pulses 100ms long at 1000 V/cm. Irreversible electroporation was used in rabbit distal femur condyles and in sheep vertebral body by applying 120 pulses 100ms long at 1750 V/cm. Any effect on surrounding sensitive structures was investigated. Reversible electroporation of sciatic nerve was associated with transient foot functional deficit that completely recovered at 30 days. Irreversible electroporation removed cells from trabeculae in the femurs of rabbits and in the vertebral body of sheep. After irreversible protocol, histology and microtomography demonstrated that the trabecular structure was maintained, the presence of new bone marrow cells, osteoblasts, and mineral apposition characterized by new trabeculae thinner than controls (P = .005) and a significant reduction in the ablated areas (-225%, P = .0219). Spinal cord, vertebral pedicles and spinal nerves showed transient edema in the absence of functional or structural alterations. Collectively, these results show that electroporation can be safely applied to bone even in the proximity of neuronal structures.

Histological, Histomorphometrical, and Biomechanical Studies of Bone-Implanted Medical Devices: Hard Resin Embedding

“…At higher magnification, it is possible to see the presence of newly formed bone in the whole trabecular bone around the electrodes, thus highlighting that the insertion procedure does not influence bone tissue viability. In fact, preexisting trabeculae among the electrodes were covered by osteoblasts (OBs) with evident evenly spread osteocytes [11]. A hydroxyapatite-coated titanium implant ( Figure 3) was implanted in a rabbit femoral condyle.…”

“…In the images, the double labeling of bone trabeculae is well evidenced. e length of fluorescent lines and the distance between each other are measurable parameters which can be used to evaluate bone turnover [11,15].…”

Electrochemotherapy of Spinal Metastases Using Transpedicular Approach—A Numerical Feasibility Study

“…Preclinical studies have demonstrated that in contrast to other ablative techniques, irreversible electroporation does not affect bone structure in the long term. 16 , 17 , 19 It only affects the cell membrane, while the tissue scaffold remains intact, thus preserving the mechanical competence of treated bone. Furthermore, irreversible electroporation does not affect or prevent osteogenic activity.…”

“…There are extensive studies on electroporation thresholds for specific tissues, such as liver, muscle, and brain, and on tumors present in these tissues, 25 , 26 , 32 , 43 , 44 but only a few preclinical studies on the effect of electroporation on bone and nerve tissue. 17 , 19 , 27 , 45 , 46 Thresholds for bone, bone tumors, and spinal cord have not yet been determined. Reported results on thresholds for electroporation of tumor tissue vary, depending on tumor histology and pulse parameters.…”

“…In order to develop a numerical model that reflects the conditions in the vertebral column as close as possible, we conducted a numerical study to determine the increase in electrical conductivity due to electroporation for bone and tumor tissue. Two sets of experimental data, published in previous studies, 17 , 18 were used for this purpose.…”